The present invention relates generally to nervous stimulation implantable devices. It relates more particularly, but is not limited to, an implant for delivering vagus nerve stimulation therapies, called VNS (Vagus Nerve Stimulation) therapies.
A nerve has many axons that innervate various organs and muscles of the human body. Some of these axons innervate the organ, muscle or structure intended to be subjected to therapy, whereas others innervate organs, muscles or structures which are not affected by the therapy.
Thus an overall, undifferentiated stimulation of a nerve may, beyond the desired therapeutic effect, induce undesirable effects in other organs, muscles or sensory feedback. Moreover, to have the desired therapeutic effect via the concerned axons, a non-differentiated excitation of all nerve fibers may require a much higher electric current than is necessary for the sought therapeutic effect.
It is consequently important to deliver a spatially selective stimulation of the target organ (typically, but not limited to, a nerve such as the vagus nerve) to achieve a focused effect on targeted physiological parameters while limiting side effects on non-targeted organs or muscles and while limiting the electrical current required for stimulation.
The therapy may be delivered according to various methods—all included in the scope of the present invention—by a neurostimulation lead disposed around, near or within the targeted structure. In the most common case, the lead consists of a cuff wrapped around a nerve, such as the vagus nerve. This cuff is provided with a plurality of electrodes which are applied against the inner surface of the nerve to selectively stimulate some regions thereof, by a controlled distribution of the currents applied to the various electrodes.
The following description will mainly refer to this mode of delivery of nerve stimulation therapy, but it is understood that it does not present a limitation. The invention is applicable as well to other types of leads, including tubular, stent-shaped leads introduced inside a vessel, for example the aorta, to stimulate some baroreceptor sites that have an indirect effect on the nervous system, or implanted leads directly inside the organ, typically a nerve or brain, for direct, in situ, stimulation of the nervous system.
A number of attempts to perform an advanced stimulation, or for particular applications, of certain nerve fibers have been described. In particular:
US 2012/065702 A1 describes a stimulation device with multiple electrodes for multiple stimulation, with priority management in function of the motor response;
WO 2009/025817 A2 and WO 2009/020639 A1 disclose a stimulator capable of assessing the response of a patient to various possible stimulation electrode configurations, including intracardiac electrodes, based on various criteria evaluated from physiological signals collected by sensors to determine the configuration providing the best therapy;US 2014/0005739 A1 describes a neurostimulator capable of assessing the response of a patient to various possible electrode configurations, on the basis of an analysis of the patient's heart rhythm;The article of Ordelman et al. “Selectivity for Specific Cardiovascular Effects of Vagal Nerve Stimulation With a Multi-Contact Electrode Cuff,” IEEE Transactions on Neural Systems and Rehabilitation Engineering, Vol. 21, No. 1, January 2013, teaches the application of a bipolar stimulation with several pairs of contacts on a channel electrode;WO 2011/040842 A1 discloses a cardiac stimulation device in which a series of stimulation electrodes are powered by respective conductors. A pulse generator applies pulses to different pairs of electrodes so as to perform stimulation according to several modes;The notice #P02216 published by the Johns Hopkins University Applied Physics Laboratory, entitled “Electrode Array to Determine Specific Axonal Firing in a Peripheral Nerve” aims at identifying the fiber to stimulate by examining the response signals of the different fibers;The article from Tyler and Durand “Functionally Selective Peripheral Nerve Stimulation With a Flat Interface Nerve Electrode,” IEEE Transactions on Neural Systems and Rehabilitation Engineering, Vol. 10, No. 4, December 2002, offers a new electrode geometry for selective stimulation;WO 2004/103455 A and WO 03/099377 A teach a unidirectional stimulation with a multipolar electrode for a cardiac application, so as to neutralize some induced effects;US 2011/0301658 A tests different stimulation parameters and different positions of electrodes to identify certain nerve fibers during the surgical phase; it does not address an implantable autonomous stimulation device;US 2012/0239109 A1 describes a quadripolar configuration of anodes for epidural stimulation for the treatment of pain;US 2012/0065699 A1 describes a DBS (Deep Brain Stimulation) lead having a plurality of independently powered stimulation electrodes, as well as collection electrodes. The purpose is to target a given area by adjusting the pacing configuration, particularly to reduce the device consumption while providing methods of collection of a local signal;U.S. Pat. No. 7,483,747 B2 discloses a nerve stimulation system with optimized consumption and the effectiveness of the implant, but by methods of stimulation profiles and parameters and not of electrode configurations;US 2013/0165994 A1 describes a VNS lead with possibility of switching from one set of electrodes to the other to maintain the efficiency of the stimulation to avoid habituation or by readjusting the targets after a displacement of the VNS lead.
However, none of these proposals allows an optimization of the electrode configuration of a neurostimulator that takes into account the following three aspects: i) Consumption of the implant, which must be controlled very strictly for not burdening the life of the implant; ii) Maximization of the physiological effect produced by the neurostimulation therapy; and iii) Minimization of undesirable side effects induced by stimulation of the nerve (e.g. cough triggering).